Omar_2026_Sci.Rep_16_

Alzheimer's disease, the leading cause of dementia, is strongly associated with impaired cholinergic neurotransmission due to excessive acetylcholine degradation by acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Because current medications provide only symptomatic relief without modifying disease progression, there is an urgent need for more effective therapeutic agents. Dual inhibitors targeting both AChE and BChE represent a promising strategy. In this study, we designed and synthesized a novel series of benzimidazol-alkanesulfonate conjugates (4a-r) and evaluated their dual inhibitory activity against AChE and BChE. The results indicated that most compounds exhibited moderate to high inhibitory activity toward the target enzymes; however, derivatives 4b, 4h, 4i, 4q, and 4r showed promising AChE inhibitory activity with IC(50) values of 0.91 +/- 0.02, 0.89 +/- 0.02, 0.54 +/- 0.05, 0.37 +/- 0.01, and 0.41 +/- 0.009 microM, respectively, comparable to that of the reference drug donepezil (IC(50) = 0.67 +/- 0.00 microM). The antioxidant potency (represented by TAC and IRP) and scavenging activity (represented by DPPH, ABTS, NO, OH, and H(2)O(2)) revealed that compounds 4q and 4r possess remarkable antioxidant potential, comparable to the reference antioxidant ascorbic acid. Furthermore, in silico ADME prediction and molecular docking studies were performed to predict their binding modes and interactions in the AChE binding pocket; the results revealed that derivatives 4q and 4r showed the highest binding affinity among the tested series and the reference drug donepezil, which validated the obtained in vitro results.